Theoretical analysis of human muscle membrane behavior in hypokalemic periodic paralysis

Computer simulations were performed to investigate the behavior of human muscle membrane with membrane defects supposed to be present in the muscular disease Hypokalemic Periodic Paralysis (HOPP). The model used for simulation was a Hodgkin-Huxley model. The T-tubular system was also incorporated. It was studied whether the membrane defects caused the following recorded HOPP phenomena: a slight depolarization of a HOPP muscle cell when serum potassium is normal and a strong depolarization to -50 mV when serum potassium is low. In the authors´ model a constant small sodium leak conductance slightly depolarized the cell, whereas a small fraction of noninactivating sodium channels caused a strong depolarization. In the case of a dependency of this fraction on serum potassium according to a Boltzmann relation such a depolarization occurred only when serum potassium was low. In the authors´ simulations, the resting membrane potential moved from -90 mV to -30 mV after a single action potential when 8%, or more of the sodium channels did not inactivate. The authors´ results were qualitatively similar when the T-tubular system was decoupled